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Microbes and plants can produce unpredictably structured organic molecules (known as natural products), which have initiated and inspired many drugs and agrochemicals.Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many gene clusters are silent under standard cultivation conditions.Over two thousand alkaloidal phytochemicals such as morphine, camptothecin and reserpine are biosynthesized by strictosidine synthetase (STR) through Pictet-Spengler (PS) reaction.A comparative genomic analysis has clarified that Chaetomium globosum has a STR-like gene (FPS gene), but remain silent or poorly activated in the laboratory cultivations since no PS-derived secondary metabolite has been detected in the fungal culture.Therefore, the author of Prof.R.X.Tan's group adopted a C.globosum strain to test for the activation of its "unworking" PS-based biosynthetic machinery.As a result, 1-methyl-L-tryptophan (1-MT) was demonstrated to be able to up-regulate the FPS expression and condense with the fungal aldehyde flavipin to form "unnatural"natural products (named chaetoglines A-H) with unprecedented skeletons, of which chaetoglines B and F are potently antibacterial with the latter inhibiting acetylcholinesterase.